Nature Medicine9, 1363 - 1369 (2003)
Published online: 12 October 2003; | doi:10.1038/nm947
Hepatocyte growth factor and its receptor are required for malaria infection
Margarida Carrolo1, Silvia Giordano3, Laura Cabrita-Santos1, 2, Simona Corso3, Ana M Vigário1, Susana Silva1, Patricia Leirião1, Daniel Carapau1, Rosario Armas-Portela4, Paolo M Comoglio3, Ana Rodriguez2
& Maria M Mota1
1
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
2
New York University School of Medicine, Department of Medical and Molecular Parasitology, 341 E 25th Street, New York, New York 10010, USA.
3
Institute for Cancer Research and Treatment, University of Torino School of Medicine, Strada Provinciale 142, 10060 Candiolo (Torino), Italy.
4
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Plasmodium, the causative agent of malaria, must first infect hepatocytes to initiate a mammalian infection. Sporozoites migrate through several hepatocytes, by breaching their plasma membranes, before infection is finally established in one of them. Here we show that wounding of hepatocytes by sporozoite migration induces the secretion of hepatocyte growth factor (HGF), which renders hepatocytes susceptible to infection. Infection depends on activation of the HGF receptor, MET, by secreted HGF. The malaria parasite exploits MET not as a primary binding site, but as a mediator of signals that make the host cell susceptible to infection. HGF/MET signaling induces rearrangements of the host-cell actin cytoskeleton that are required for the early development of the parasites within hepatocytes. Our findings identify HGF and MET as potential targets for new approaches to malaria prevention.
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